title: Effect of polymers and media type on extending the dissolution of amorphous pioglitazone and inhibiting the recrystallization from a supersaturated state.
abstract: Amorphous forms of crystalline drug are widely utilized for bioavailability enhancement of low solubility drugs in the pharmaceutical industry. Polymers have been found to be effective crystallization inhibitors for amorphous forms in solid states during storage or in liquid states during dissolution process. The dissolution and crystallization behaviors of these amorphous forms in the presence or absence of polymers are still far from adequately understood especially in different dissolution environments. The objective of this study was to investigate the effects of polymers and media type on extending the dissolution of amorphous pioglitazone and inhibiting the recrystallization from a supersaturated state. Polyvinylpyrrolidone K30 (PVPK30), polyvinylpyrrolidone K90 (PVPK90), polyethylene glycol 6000 (PEG6000), polyethylene-polypropylene glycol 188 (F-68), hydroxypropylmethylcellulose (HPMC) and beta-cyclodextrin (β-CD) were employed to understand these behaviors changes because these polymers were used widely. Three solutions including neutral water and phosphate buffer solutions (PBS, pH6.8 and pH7.4) were adopted as dissolution media to determine the behaviors changes comprehensively. In the presence of polymers, dissolution and solubility were extended to different degrees in three media. Polymers can delay the crystallization routes dependently of the medium type. Buffer salts in media reduced the dissolution and accelerated the crystallization process. Crystallization inhibition of these polymers was strongly dependent on the type and pH of media. HPMC displayed the strongest crystallization inhibition effects, resulting in the greatest degree of maintaining a supersaturated state that can sustain most effectively for biologically relevant timeframes.
authors.affiliation: The State Key Laboratories of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research , Tianjin , P.R. China and.
authors.forename: Nian-Qiu
authors.initials: NQ
authors.lastname: Shi
authors.forename: Jing
authors.initials: J
authors.lastname: Yao
authors.forename: Xing-Lin
authors.initials: XL
authors.lastname: Wang
mesh_terms: D001682:Biological Availability; D002021:Buffers; D003460:Crystallization; D006863:Hydrogen-Ion Concentration; D010710:Phosphates / Q000737:chemistry; D000077205:Pioglitazone; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D012996:Solutions / Q000737:chemistry; D045162:Thiazolidinediones / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D002021:Buffers; D010710:Phosphates; D011108:Polymers; D012996:Solutions; D045162:Thiazolidinediones; D014867:Water; D000077205:Pioglitazone
keywords: Amorphous forms; crystallization; dissolution; polymers; supersaturated state